Patent GB-782354-A (GB)
Title: Improvements in or relating to the manufacture of vitamin a
Filed: 1953-12-07
Abstract: Vitamin A is prepared by condensing betaionone with a monohalogen acetic ester by Reformatsky reaction, converting the hydroxy ester obtained or its dehydration product, after saponification, into an acid halide of betaionylidene acetic acid by means of a halogenating agent capable of converting a carboxylic acid to the corresponding acid halide, converting the acid halide into the corresponding alcohol, b -vinylidene ethanol, by means of a complex metal hydride containing two different metal atoms, converting this into the C18-ketone by known methods, condensing with a monohalogen acetic ester by Reformatsky reaction, converting the hydroxy ester or its dehydration product, after saponification into Vitamin A acid halide, by means of a halogenating agent capable of converting a carboxylic acid into the corresponding acid halide and converting the acid halide into Vitamin A by means of a complex metal hydride containing two different metal atoms.  The halogenation reactions are suitably carried out by treating the acids obtained by saponification of the Reformatsky reaction product with phosphorus trichloride, pentachloride or tribromide in a solvent, for example in benzene, toluene or xylene at 50 DEG  to 70 DEG  C. or in chloroform at -50 DEG  to 0 DEG  C.  The treatment with phosphorus halides may be used to effect both dehydration and halogenation, or, if desired, the dehydration may be effected separately, for example by treating a solution of the hydroxy acid in benzene with iodine.  The conversion of the acid halides to the corresponding alcohols is suitably effected by reaction of lithium aluminium hydride, sodium boron hydride or magnesium aluminium hydride at a temperature below 5 DEG C. either on the acid halide itself or upon an ester of the corresponding carboxylic acid obtained from the halide.  The conversion of the beta-ionylidene ethanol into the C18-ketone is suitably carried out by oxidizing the alcohol with manganese dioxide to form betaionylidene acetaldehyde and condensing this substance with acetone, preferably under alkaline conditions, for example in the presence of dilute caustic soda, to form the C18-ketone.  In an example, beta-ionol acetic acid ethyl acetate, prepared from beta-ionone and ethyl bromoacetate by Reformatsky reaction is treated with iodine in benzene to give the "iso" C15 acid ethyl ester which is saponified to the free acid, treated with phosphorus trichloride to give beta-ionylidene acetic acid chloride reduced with lithium aluminium hydride to give beta ionylidene ethanol, oxidized with manganese dioxide to beta-ionylidene acetaldehyde and treated with acetone to give the C18-ketone, condensed with ethyl bromoacetate by Reforatsky reaction to give the hydroxy C20 acid ethyl ester, which is treated with iodine in benzene to give the "iso" C20 acid ethyl ester, saponified, converted to the acid chloride by reaction with PCl3 and reduced with lithium aluminium hydride to give Vitamin A. Specifications 744,804 and 751,753 are referred to.  Reference has been directed by the Comptroller to Specification 668,604.